tbuckley/cabot-search huggingface dataset:
Abstract 15114: Estimation of Left Ventricular Filling Pressure Using Left Atrial Strain in Coarctation of Aorta
Authors: OMAR ABOZIED, Ahmed Goda, Dhanya Ramachandran, Kartik Andi, Alexander C Egbe
Journal: Circulation (2022)

Background: Left atrial (LA) reservoir strain &lt;18% and booster strain &lt;8% have been proposed as the optimal threshold to detect increased left ventricular (LV) filling pressure in patients with acquired heart disease. This study aimed to determine whether these LA strain cut-off points can detect increased LV filling pressure in adults with coarctation of aorta (COA). Methods: Retrospective study of adults with COA (n=126; age 36±16 years), that underwent non-simultaneous cardiac catheterization and echocardiography. Increased LV filling pressure was defined as pulmonary artery wedge pressure (PAWP) &gt;12 mmHg or LV end-diastolic pressure (LVEDP) &gt;16 mmHg. Results: The median PAWP was 13 (11-18) mmHg, and had a good correlation with LA reservoir strain (r=-0.69, p&lt;0.001) and LA booster strain (r=-0.61, p&lt;0.001). LA reservoir strain &lt;18% had superior diagnostic power to detect PAWP &gt;12 mmHg as compared to LA volume index &gt;34 ml/m2, septal E/e’ &gt;15, lateral E/e’ &gt;13, and tricuspid regurgitation velocity &gt;2.8 m/s (p&lt;0.05 for all). The median LVEDP was 17 (14-20) mmHg, and LVEDP had a modest correlation with LA reservoir strain (r=-0.39, p&lt;0.001) and LA booster strain (r=-0.33, p=0.002). LA reservoir strain &lt;18% had superior diagnostic power to detect LVEDP &gt;16 mmHg as compared to LA volume index &gt;34 ml/m2, septal E/e’ &gt;15, lateral E/e’ &gt;13 and tricuspid regurgitation &gt;2.8 m/s (p&lt;0.05 for all). Conclusions: These data suggest that LA strain could be used to identify patients with increased LV filling pressure thereby improving patient selection for cardiac catheterization and interventions.
Abstract 14255: Effectiveness and Safety of Ticagrelor versus Clopidogrel in Acute Coronary Syndrome: A Meta-Analysis of Real - World Data
Authors: Sara Al-Balushi, Alaa Rahhal, Mohamed Abdelghani, Mohammed Awad Ashour, Yazan Al-Mohtasib, Abdul R Abid, JASSIM ALSUWAIDI
Journal: Circulation (2022)

Background: Ticagrelor, a potent P2Y12 inhibitor, was superior to clopidogrel in preventing mortality post acute coronary syndrome (ACS) without a major safety concern in the PLATO trial. Nevertheless, the real-world evidence of ticagrelor post ACS is conflicting and inconclusive. Therefore, we conducted a meta-analysis to assess the effectiveness and safety of ticagrelor versus clopidogrel post ACS using real-world data. Methods: We performed a meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed to identify observational studies exploring the effectiveness and safety of ticagrelor and versus clopidogrel in ACS until 12/01/2022. Two independent reviewers assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data. Effectiveness outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), and stent thrombosis. Safety outcomes included major bleeding, gastrointestinal (GI) bleeding, and dyspnea. Results: A total of 26 observational studies comparing ticagrelor to clopidogrel post ACS were included. Compared to clopidogrel, ticagrelor significantly reduced all-cause mortality (odds ratio [OR], 0.68 [95% CI, 0.58-0.81], I 2 = 78%)) and cardiovascular mortality (OR, 0.64 [95% CI, 0.48-0.85], I 2 = 78%). Whereas there was no statically significant difference between ticagrelor and clopidogrel in MI and stent thrombosis (OR, 0.92 [95% CI, 0.81-1.05] I 2 =56%) and (OR, 0.61 [95% CI, 0.23-1.66], I 2 = 89%), respectively. Ticagrelor was associated with significantly higher major bleeding incidence (OR, 1.21 [95% CI, 1.06-1.39], I 2 =52%). However, GI bleeding and dyspnea were not significantly increased with ticagrelor use. Conclusions: Real-world data of ticagrelor use post ACS demonstrated that ticagrelor reduced all-cause mortality and cardiovascular mortality in comparison to clopidogrel. However, it was associated with increased major bleeding. Real-world evidence with long follow-up confirming the safety of ticagrelor in comparison to clopidogrel post ACS demonstrated in controlled trials is warranted.
Abstract 15143: The Sphk1/S1P/S1PR2 Axis Regulates Pulmonary Vascular Remodeling by Activating a Mitochondrial ROS and NLRP3 Inflammasome Regulatory Loop
Authors: Yang Bai, Marta T Gomes, Clare Prohaska, Angelia Lockett, Roberto F Machado
Journal: Circulation (2022)

Introduction: Sphk1/S1P/S1PR2 axis regulated NLRP3 inflammasome and promoted pyroptosis by activating NF-κB in human PASMC. Abnormal or inappropriate ROS mediates the development of PAH modulating inflammation, proliferation, and energy metabolism. Mitochondrial ROS promotes deubiquitylation of NLRP3 and activate the inflammasome. However, the function and regulation of S1P axis mediated mitochondrial ROS and NLRP3 inflammasome in PAH remain unknown. Hypothesis: We hypothesized that S1P axis regulated pulmonary vascular remodeling by activated mitochondrial ROS and NLRP3 inflammasome. Methods: NLRP3 inflammasome and pyroptosis activation were detected in PASMC from patients with PAH. JTE013, PF543, MCC950 and MitoTEMPO were used to modulate S1P, NLRP3 inflammasome and mitochondrial ROS signaling, respectively. Activation of inflammasome and pyroptosis were detected by western blots (WB), real-time PCR or immunofluorescence (IF). IL-1β secretion was detected by ELISA. ROS were measured by Mitosox Red and DCFDA. Mitochondrial membrane potential was determined by JC-1 dye assay. PASMCs which were isolated from Sphk1 fl/fl Tagln Cre (+) and Sphk1 fl/fl mice were used to detect the role of S1P axis in vivo. Results: NLRP3 Inflammasome and pyroptosis were activated in PASMCs from patients with PAH. JTE013 or PF543 treatment inhibited NLRP3, ASC, N-GSDMD, HMGB1, cleaved IL-1β and IL-18 expression, and suppressed mitochondrial ROS, as well as mitochondrial hyperpolarization induced by S1P. Treatment with MitoTEMPO decreased S1P induced-NLRP3, ASC, N-GSDMD, HMGB1, cleaved IL-1β and IL-18 expression and inhibited IL-1β secretion. MCC950 controlled the activation of mitochondrial ROS, as well as mitochondrial hyperpolarization which were activated by S1P. NLRP3, cleaved IL-1β, ASC, HMGB1 and N-GSDMD expression were decreased in mPASMCs from Sphk1 fl/fl Tagln Cre (+) mice. Conclusions: S1P induces activation of mitochondrial ROS and NLRP3 inflammasome, and that the Sphk1/S1P/S1PR2 signaling axis may be involved in this context. Activation of the mitochondrial ROS and NLRP3 inflammasome regulatory loop may be an important mechanism underlying PAH pathogenesis, targeting of which may be exploited for the treatment of PAH.
Abstract 14817: Machine Learning Computer Vision for Point of Care Decision Support of Echocardiographic Identification of Hypertrophic Cardiomyopathy
Authors: Sreekanth Vemulapalli, Fanjie Kong, Fawaz Alenezi, Anna Giczewska, Lillian Kang, Karen Chiswell, Ricardo Henao, Andrew Wang
Journal: Circulation (2022)

Introduction: Hypertrophic cardiomyopathy (HCM) has an estimated prevalence of 1/500 but remains underdiagnosed. Echocardiography is the primary diagnostic modality but requires recognition of varied patterns of hypertrophy. Point of care tools to facilitate improved identification of HCM are needed. Methods: We identified 400 study cases of HCM in adults meeting professional society guideline diagnostic criteria from 2000-2020 at Duke University Medical Center. 900 study controls matched on age, sex, year of echo, and ejection fraction were also identified. Multi-vendor echocardiographic examinations performed within 12 months of initial diagnosis were used to train a convolutional neural network (CNN) to identify HCM. The model consisting of a 18-layer deep R(2+1)D residual network was developed on 60% of the data (training), 20% of the data (validation) was used to select model hyperparameters and to monitor for overfitting, and the remaining 20% (test) was used for performance estimation. CNN performance was evaluated by the receiving operating characteristic (ROC) and precision-recall curve and their summaries, namely, area under the ROC (AUROC) and average precision (AP, i.e. , average positive predictive value). We report performance characteristics at the study level. Results: Among 400 HCM cases and 900 controls, the median age was 65, with 48.1% male. Hypertension was present in 44.9%, with heart failure in 16.3% and Atrial Fibrillation in 12%. Median EF was 55% with 14.5% having an EF &lt; 50%. Median diastolic dimension was 4.4 cm and moderate or severe MR was present in 8.4%. Study-level AUCROC for the CNN was 0.853 and the average precision was 0.698 (Figure 1). Conclusion: A machine learning CNN is able identify study-wise HCM with an AUC of 0.853. Further work will be necessary to ensure explainability of results and similar multi-institutional performance as a point of care tool for the echocardiographic identification of HCM on diagnostic rates.
Abstract 14387: Early Atherosclerosis on CCTA: Insights From Artificial Intelligence-Enabled Quantitative CT Analysis of Serial Scans From the Paradigm Trial
Authors: Rhanderson Cardoso, James K Min, Andrew Choi, James Earls, Ron Blankstein
Journal: Circulation (2022)

Introduction: Non-obstructing small coronary plaques are not always appreciated during coronary CTA (CCTA) but may be identified by artificial intelligence-enabled quantitative CT (AI-QCT). It is unclear if these are true early atherosclerotic plaques or false positive findings. Hypothesis: Serial CCTA exams may provide insights into the natural history of these findings, as a plaque appearing in the same anatomical location and demonstrating interval change is likely real. Methods: 399 plaques measuring between 0.1 and 50.0 mm 3 were identified using AI-QCT in 83 patients with serial CCTA exams (N=166 exams) from the PARADIGM Trial. The total volume (TPV), calcified (CP), non-calcified (NCP) and low-density plaque (LD-NCP) volume, and % diameter stenosis of each plaque were recorded. Serial studies were processed in a blinded manner and linked after processing. The presence and change in plaque characteristics were assessed. Results: Overall 345/399 (86%) of small plaques were present in the same location on follow-up (mean interval 3.8 years), including 313/350 (89%) of plaques &gt;2.0mm 3 (Figure 1). Plaques were nonobstructive (&lt;=50%) in 99.5% of initial and 97.5% of follow-up studies. On follow-up, 82% (250/305) increased in size and 293/304 (96%) increased in calcified plaque content. Plaques in statin taking patients demonstrated higher median increase in CP (8.7 vs 4.0 mm 3 , p&lt;0.05) and transformed from all NCP to mixed NCP + CP at a higher rate (59.3 vs 43.9%, p=0.0027 Conclusions: Small coronary plaques depicted with serial AI-QCT are often present in the same location upon follow-up, increase in volume, and develop or increase calcification with statin therapy. While further data regarding the natural history and prognosis of these plaque is warranted, these findings provide a rationale for identifying early coronary atherosclerotic plaques.
Abstract 15145: Aldehyde Dehydrogenase 2 Agonist Reverses Fibroblast Activation in the End Stage Human Right Ventricle Failure via 3’Utr Regulation of Profibrotic Genes
Authors: Rahul Neupane, Katarzyna A Cieslik, Keith Youker, Suresh S Palaniyandi, Guha Ashrith, Rajarajan A Thandavarayan
Journal: Circulation (2022)

Background: Cardiac fibrosis, a prominent feature of pressure overloaded right ventricle (RV) in pulmonary hypertension (PH), is fundamental to the development of right ventricle failure (RVF). We found that a defect in alternative polyadenylation (APA) of profibrotic genes is a driving factor that induces fibrosis. Oxidative stress-mediated reactive aldehydes, such as 4-hydroxy-2-nonenal (4HNE) contribute to fibrosis and extracellular matrix (ECM) remodeling. However, the role of 4HNE in APA is unknown. Methods: We compared isolated cardiac fibroblasts from the RVs of explanted transplanted hearts of recipients with pulmonary hypertension patients to control hearts. Results: Compared to controls, tissue and fibroblasts derived from failing RV human hearts have greater deposition of extracellular matrix (ECM) proteins, such as collagen type I alpha (COL1A) and fibronectin (FN1), the expression of alpha smooth muscle actin (α-SMA), indicative of myofibroblast differentiation, and nuclear factor kappa B subunit (NFκB), a transcription factor critical for profibrotic genes transcriptional activation. Moreover, alternative polyadenylation (APA) isoforms of mRNA for COL1A, FN1, NFκB, TGF-β1 and its receptor - transforming growth factor beta receptor 1 (TGFβR1) are associated with shortened 3’UTR in RVF tissues or fibroblasts. Likewise, reduced expression and activity of aldehyde dehydrogenase 2 (ALDH2) expression, a 4HNE detoxifying enzyme, correlated with increased 4HNE adduction in tissues and cardiac fibroblasts derived from RVF hearts. Moreover, ALDH2 activation by its agonist, Alda-1, decreased 4HNE adduction and oxidative stress and most importantly downregulated the gene and protein expression of profibrotic genes, simultaneously lengthening the 3’UTR of the previously shortened profibrotic genes. Conclusion: In RVF, fibroblasts express mRNA of profibrotic genes with shortened 3'UTRs, suggesting the feasibility of developing antifibrotic therapies targeting 3'UTRs in myofibroblasts. Furthermore, our findings suggest that Alda-1 has a therapeutic role in mitigating cardiac fibrosis in RVF hearts by attenuating 4HNE-mediated dysregulation of APA.
Abstract 14374: Clinical and Echocardiographic Characteristics of Patients Who Develop Post Liver Transplant Non-Ischemic Cardiomyopathy
Authors: Sohaib A Basharat, Joseph Chung, SAAD KARAMAT, Dmitry Abramov, Gary E Fraser, Purvi Parwani
Journal: Circulation (2022)

Background: Non-ischemic cardiomyopathy is a well-known but poorly understood cardiac complication post orthotopic liver transplantation (OLT). Methods: We performed a nested case control study in a cohort of 590 patients who underwent OLT at Loma Linda University between 2013 - 2021. 29 (4.9%) patients developed post-OLT non-ischemic cardiomyopathy. 100 patients who did not develop cardiomyopathy were selected randomly from the cohort to serve as control group. Clinical characteristics of cases and controls were compared and echocardiograms of patients who developed cardiomyopathy reviewed. Results: Patients who developed cardiomyopathy were more likely to be female, less likely to have history of hypertension, had lower baseline hemoglobin and platelets, and higher MELD scores ( Table 1) . Mean pre-transplant ejection fraction (EF) was 69% among patients who developed cardiomyopathy. Cardiomyopathy developed on average 10 days after OLT with mean EF dropping to 26%. 24 (83%) patients had reduced EF (&lt;40%) and 5 (17%) had mid-range EF (40-49%). Wall motion analysis revealed global hypokinesis in 11 (38%) patients, mid-ventricular takotsubo in 11 (38%) patients, apical takotsubo in 5 (17%) patients, and basal takotsubo in 2 (7%) patients (Figure 1) . 24 (83%) patients recovered EF (≥ 50%) on average of 113 days after initial diagnosis of cardiomyopathy. Conclusions: Female sex and higher MELD scores were associated with development of non-ischemic cardiomyopathy post OLT. Global hypokinesis and mid-ventricular takotsubo were the most common patterns of wall motion abnormality. EF recovery was noted in majority of patients indicating operative stress related etiology.
Abstract 14316: Prognostic Utility of Left Atrial Strain to Predict Thromboembolic Events and Mortality in Patients With Amyloid Cardiomyopathy
Authors: Emmanuel O Akintoye, Muhammad Majid, Mazen A Hanna, Allan L Klein
Journal: Circulation (2022)

Introduction: There is no risk stratification tool to identify patients with amyloid cardiomyopathy (ACM) that will benefit from prophylactic anticoagulation and the available survival staging systems have only modest discriminatory ability Methods: Using the prospective Amyloid Heart Disease database of Cleveland Clinic, we identified patients with light chain (AL) or transthyretin (ATTR) ACM but no history of atrial fibrillation. LA strain was measured in accordance with guidelines and its association with incident thromboembolic event (TE) and mortality was evaluated. In addition, we determined the incremental utility of LA strain to current ACM prognostic staging systems Results: In 448 patients (mean age 68 years, 72% male), there were 64 (14.3%) TE and 234 deaths (52.2%) after a median follow up of 3.8 years. LA reservoir (LAr) and contractile (LAc) strain significantly predict both events ( Fig 1 ). The hazard ratio (HR) for TE was 2.22 (95% CI=1.27-3.85, p=0.006) and 2.63 (1.25-5.00, p=0.01) per standard deviation decrease in LAr and LAc, respectively. The respective HR for mortality was 1.32 (1.09-1.59, p&lt;0.001) and 1.49 (1.22-1.75, p&lt;0.001). The addition of either LAr or LAc to prognostic staging systems resulted in significant increase in discriminatory ability e.g., C-statistics of the revised Mayo staging for AL increased from 0.65 to 0.68 and 0.70 (p≤0.02) after the addition of the LAr and LAc, respectively ( Fig 2 ) Conclusions: Patients with ACM experience high rate of TE and mortality, even in the absence of atrial fibrillation. LA strain can help to identify those that will benefit from prophylactic anticoagulation and provides incremental risk stratification
Abstract 14241: Feasibility and Safety of Non-Contrast Optical Coherence Tomography Imaging Using Hydroxyethyl Starch in Coronary Arteries
Authors: Dong Oh Kang, Hyeong Soo Nam, Sunwon Kim, Hongki Yoo, Jin W Kim
Journal: Circulation (2022)

Background/Objectives: Contemporary high-resolution intracoronary optical coherence tomography (OCT) requires injection of flushing media for image acquisition. There is a growing need for an alternative flushing media other than iodine contrast to reduce the risk of acute kidney injury. To address this issue, we investigated the safety and feasibility of hydroxyethyl starch (pentastarch) as a flushing media for OCT image acquisition and compared with the contrast media flushed images. Methods: We prospectively enrolled 43 patients with 70 coronary lesions (46 stented and 24 pre-stented or non-culprit lesions). Paired OCT images were obtained by manual injection of iodine contrast (average 12 mL), followed by pentastarch (average 15 mL). A total of 162 runs (81 pairs) were analyzed and each OCT pullback was assessed on a frame-by-frame basis by automated customized lumen contour and stent strut segmentation algorithm. Results: Image quality as assessed by proportion of clear image segments were comparable between the contrast media and pentastarch flushed images (93.3% vs. 93.7%; p=0.501). Pixel-based flushing capability showed no significant difference between the paired image segments (median(IQR), 0.951(0.947-0.953) vs. 0.951(0.949-0.952), p=0.264; Figure). Quantitative measurements of minimal stent area (R 2 =0.977, p&lt;0.001), minimal lumen area (R 2 =0.983, p&lt;0.001) correlated well between the paired OCT runs. There were no clinically relevant complications associated with OCT imaging with pentastarch such as anaphylaxis, life-threatening arrhythmia, or acute renal deterioration. Conclusions: Intracoronary OCT using pentastarch is safe and technically feasible without affecting the optical signal intensity and overall image quality. Non-contrast imaging with pentastarch significantly reduces the obligatory iodine contrast load, therefore, could be considered as a promising strategy in high-risk patients for renal impairment.
Abstract 14304: Does QRS Fragmentation Have a Role in Risk Stratification for Sudden Death in Hypertrophic Cardiomyopathy?
Authors: Rachael Studley, Christopher Madias, Nadia Bokhari, Erick Quintana, Chen Bao, Barry Maron, Martin Maron, Ethan J Rowin
Journal: Circulation (2022)

Background: Fragmentation of the QRS complex on 12-lead electrocardiogram (ECG) represents alterations of myocardial activation due to myocardial scarring and has been associated with increased risk for sudden death and adverse prognosis. However the clinical significance of this finding in hypertrophic cardiomyopathy (HCM) remains unresolved. Methods: Consecutive HCM patients evaluated from 2004 to 2020 were included and followed for 5.1 ± 4.1 years for outcomes including sudden death events (appropriate ICD interventions for VT/VF, cardiac arrest, or sudden death) and development of endstage heart failure requiring transplant. QRS fragmentation was defined as presence of an additional R wave or notching in the R or S wave in two contiguous ECG leads in the absence of bundle branch block. Results: Among 1929 HCM patients, 539 (28%) were identified with QRS fragmentation. As compared to patients without QRS fragmentation, patients with QRS fragmentation had similar baseline demographics including age (52±16 vs. 53±16, p=0.35), gender (60% vs. 61% male, p=0.51), ejection fraction (64 ± 6 vs. 64 ± 5, p=0.77) and presence of LV outflow obstruction (≥30mmHg at rest or provocation; 65% vs. 65%, p=0.9). While patients with QRS fragmentation had more substantial LV hypertrophy (19 ± 4 vs. 18 ± 4, p=0.001) as well as presence and extent of late gadolinium enhancement by cardiac MRI (64% vs. 56%, 6.3 ± 6 vs. 5 ± 5, p&lt;0.01), there was no difference in other risk markers including syncope (9% vs 9%, p=0.89), family history of SD (8% vs. 6%, p=0.31), NSVT (10.5% vs. 8%, p=0.10). Over follow-up, patients with QRS fragmentation were at increased risk for sudden death events (5.6% vs. 2.2%, p&lt;0.001) and development of end-stage heart failure requiring transplant (2.4% vs. 0.8%, p=0.007). However, sensitivity and positive predictive value of QRS fragmentation for predicting sudden death events (50% and 5.6%, respectively) as well as endstage heart failure (52% and 2.4%) is limited. Conclusion: In a large consecutive HCM cohort, QRS fragmentation on 12-lead ECG is associated with extreme HCM phenotype and a number of adverse consequences including sudden death events and endstage development, and represents a potential prognostic marker.